INTRODUCTION: The incidence of SARS-CoV-2 re-infection has not been widely evaluated in low-income and middle-income countries. Understanding immune responses elicited by SARS-CoV-2 natural infection and factors that lead to re-infection in a community setting is important for public health policy. We aim to investigate the risk of primary infection and re-infection among those without and with evidence of prior infection as defined by the presence of antibodies to SARS-CoV-2 spike protein.

METHODS AND ANALYSIS: A baseline seroprevalence survey will test for SARS-CoV-2 antibodies among healthy adults in Vellore, India. Based on an expected seropositivity rate of 50% in the general population, with annual attack rates of 12%, 6%, 4.8% and 4% among those unvaccinated and seronegative, vaccinated and seronegative, unvaccinated and seropositive, and vaccinated and seropositive, respectively, we will recruit 1200 adults who will be followed up for a total of 24 months. Weekly self-collected saliva samples will be tested by reverse transcription-PCR (RT-PCR) to detect SARS-CoV-2 infections, for a period of 1 year. For any person testing RT-PCR positive, blood samples will be collected within 2 days of RT-PCR positivity and on days 30 and 90 to assess the kinetics and longevity of the antibody responses, B cell memory and T cell memory post-infection. The data will be analysed to estimate seroprevalence at baseline and over time, the risk factors for infection, rates of primary infection and re-infection, and provide a comparison of the rates across groups based on infection and vaccination status.

ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board (IRB No: 13585) of Christian Medical College and Hospital, Vellore. The results of the study will be made available through journal publications and conference presentations.

TRIAL REGISTRATION NUMBER: Central Trial Registry of India: CTRI/2020/11/029438.